Much circumstantial evidence has been reported which links bacterial endotoxins to the etiology of inflammatory periodontal disease. However, precise data proving more than just a casual relationship between endotoxin and periodontal disease is unavailable. Before definitive correlations can be made between endotoxin and the periodontal disease process, certain key problems must be resolved. These problems include determining the ability of endotoxin to: (1) penetrate intact gingival sulcular epithelium, (2) induce chronic periodontal inflammation with associated bone loss, (3) activate the complement system in vivo (i.e. in gingival tissues). A number of methods will be employed to study these problems in the beagle dog. 1. Gingival penetration will be examined by means of radiolabeling techniques. 2. The induction of inflammation by chronic application of endotoxin will be studied using classical histologic techniques, as well as clinical inspection and radiographic procedures. 3. The role of complement will be determined by assaying for the production of complement derived chemotactic factors. Decomplementation of serum in vivo will further elucidate the importance of complement-endotoxin interaction.